It has been some time since medical procedures, namely regeneration medicine, for replacing cells that have been lost from tissue for some reason have attracted attention as a fundamental treatment for diseases. In recent years, the concept of cell drugs, which aim to regenerate and repair tissue in a disease site via the interaction of intercellular bioactive substances by injecting stem cells or precursor cells of tissue cells, has been further broadened.
In response to these circumstances, there have been many reports that differentiated cells in tissue, e.g., peripheral blood-derived monocytes, dedifferentiate into stem cells when cultured in the presence of specific cytokines.
However, when stem cells or tissue precursor cells, as a cell drug, are administered to a living body, the percentage of cells arriving at the target damaged area is not always high and is not constant. This problematically necessitates the preparation of a large amount of cells. Further, the behavior of cells that are distributed in areas other than the target area has not yet been studied in detail, and there remains a problem of side effects. Moreover, although administration of a large amount of cells is necessary for an enhanced therapeutic effect, it seems difficult to obtain autologous cells in a short period of time.
It has recently become evident that a phenomenon called homing occurs. This is a phenomenon in which SDF1 (stromal cell-derived factor 1) or VEGF (vascular endothelial cell growth factor) is expressed in a damaged area under ischemic conditions; as part of the biological repair system, these factors serve as inducible molecules; and cells expressing receptors corresponding to these inducible molecules are drawn to the damaged area. Receptors for these factors are CXCR4 for SDF1 and VEGFR for VEGF. For example, Non-Patent Document 1 reports that a wound does not heal when SDF1 is blocked in the ischemic area or when CXCR4-expressing cells are removed from the blood.
Fändrich (Non-Patent Document 2), Huberman (Non-Patent Document 3), etc., report techniques of obtaining stem cells with pluripotency from human monocytes by inducing dedifferentiation. These techniques use various cytokines, including M-CSF, for incubation. Each culture method showed that some undifferentiated markers became positive. Additionally, Kuwana et al. (Non-Patent Document 4) reports that multipotential stem cells (MOMC) can be induced from human mononuclear cells using a culture plate to which fibronectin is applied.